Organic bismuth derivatives for X-ray imaging

Abstract

An organic bismuth derivative represented by formula (I) or its salt: wherein X 1 is YNR 1 R 2 (wherein Y is --SO 2 -- or --C(O)--, R 1 is a C 3-6 alkyl group which have from 2 to 5 hydroxyl groups which may be protected, and R 2 is a hydrogen atom, a C 1-6 alkyl group or a C 1-5 acyl group which may have from 1 to 5 hydroxyl groups which may be protected, or R 1 and R 2 , together with each other, represent a C 2-6 cyclic alkylene which may have from 1 to 4 hydroxyl groups which may be protected), and each of X 2 and X 3 is, independently of each other, a hydrogen atom, a C 1-4 alkyl group, a C 1-4 alkoxy group, a C 1-4 alkylsulfonyl group, a C 1-4 alkylcarbonyl group, a nitro group, a cyano group or the same as defined for X 1 !.

We claim: 
     
       1. An organic bismuth derivative represented by formula (I) or its salt: ##STR20## wherein X 1  is YNR 1  R 2 , wherein Y is --SO 2  -- or --C(O)--, R 1  is a C 3-6  alkyl group having from 2 to 5 hydroxyl groups, optionally being protected, and R 2  is a hydrogen atom, a C 1-6  alkyl group or a C 1-5  acyl group which optionally contains from 1 to 5 hydroxyl groups optionally being protected, or R 1  and R 2 , together with each other, represent a C 2-6  cyclic alkylene which optionally contains from 1 to 4 hydroxyl groups which optionally is protected, and each of X 2  and X 3  is, independently of each other, a hydrogen atom, a C 1-4  alkyl group, a C 1-4  alkoxy group, a C 1-4  alkylsulfonyl group, a C 1-4  alkylcarbonyl group, a nitro group, a cyano group or the same as defined for X 1 . 
     
     
       2. The organic bismuth derivative or its salt according to claim 1, wherein each of X 2  and X 3  is, independently of each other, a hydrogen atom or YNR 1  R 2  wherein Y is --SO 2  -- or --C(O)--, R 1  is a C 3-6  alkyl group which have from 2 to 5 hydroxyl groups optionally being protected, and R 2  is a hydrogen atom, a C 1-6  alkyl group or a C 1-5  acyl group optionally having from 1 to 5 hydroxyl groups which optionally is protected, or R 1  and R 2 , together with each other, represent a C 2-6  cyclic alkylene optionally having from 1 to 4 hydroxyl groups optionally being protected. 
     
     
       3. The organic bismuth derivative or its salt according to claim 1, wherein R 1  is a C 3-6  alkyl group which has 2 hydroxyl groups optionally being protected, and R 2  is a hydrogen atom, a C 1-6  alkyl group or a C 1-5  acyl group optionally having from 1 to 2 hydroxyl groups optionally being protected, or R 1  and R 2 , together with each other, represent a C 2-6  cyclic alkylene optionally having from 1 to 4 hydroxyl groups optionally being protected. 
     
     
       4. The organic bismuth derivative or its salt according to claim 1, wherein each of X 2  and X 3  is, independently of each other, a hydrogen atom or YNR 1  R 2  wherein Y is --SO 2  -- or --C(O)--, R 1  is a C 3-6  alkyl group which has two hydroxyl groups optionally being protected, and R 2  is a hydrogen atom, a C 1-6  alkyl group or a C 1-5  acyl group optionally having from 1 to 2 hydroxyl groups optionally being protected, or R 1  and R 2 , together with each other, represent a C 2-6  cyclic alkylene optionally having from 1 to 4 hydroxyl groups optionally being protected. 
     
     
       5. The organic bismuth derivative or its salt according to claim 1, wherein Y is --SO 2  --. 
     
     
       6. The organic bismuth derivative or its salt according to claim 1, wherein each of X 2  and X 3  is, independently of each other, a hydrogen atom or YNR 1  R 2  wherein Y is --SO 2  --, R 1  is a C 3-6  alkyl group which has from 2 to 5 hydroxyl groups optionally being protected, and R 2  is a hydrogen atom, a C 1-6  alkyl group or a C 1-5  acyl group optionally having from 1 to 5 hydroxyl groups optionally being protected, or R 1  and R 2 , together with each other, represent a C 2-6  cyclic alkylene optionally having from 1 to 4 hydroxyl groups optionally being which may be protected. 
     
     
       7. A process of producing the organic bismuth derivative or its salt according to claim 1, which comprises reacting a reactive metal compound represented by formula (II): ##STR21## wherein X 1  is YNR 1  R 2 , wherein Y is --SO 2  -- or --C(O)--, R 1  is a C 3-6  alkyl group which has from 2 to 5 hydroxyl groups optionally being protected, and R 2  is a hydrogen atom, a C 1-6  alkyl group or a C 1-5  acyl group optionally having from 1 to 5 hydroxyl groups optionally being protected, or R 1  and R 2 , together with each other, represent a C 2-6  cyclic alkylene optionally having from 1 to 4 hydroxyl groups optionally being protected, each of X 2  and X 3  is, independently of each other, a hydrogen atom, a C 1-4  alkyl group, a C 1-4  alkoxy group, a C 1-4  alkylsulfonyl group, a C 1-4  alkylcarbonyl group, a nitro group, a cyano group, or the same as defined for X 1 , and M is MgX' wherein X' is a halogen atom or an alkali metal with a trihalobismuth compound represented by formula (III):   BiX.sub.3                                                  (III),     wherein X is a halogen atom.   
     
     
       8. A process of producing an organic bismuth derivative represented by formula (I-1) or its salt: ##STR22## wherein each of X 2  and X 3  is, independently of each other, a hydrogen atom, a C 4  alkyl group, a C 1-4  alkoxy group, a C 1-4  alkylsulfonyl group, a C 1-4  alkylcarbonyl group, a nitro group, a cyano group or YNR 1  R 2 , wherein Y is --SO 2  -- or --C(O)--, R 1  is a C 3-6  alkyl group which has from 2 to 5 hydroxyl groups optionally being protected, and R 2  is a hydrogen atom, a C 1-6  alkyl group or a C 1-5  acyl group optionally having from 1 to 5 hydroxyl groups optionally being protected, or R 1  or R 2 , together with each other, represent a C 2-6  cyclic alkylene optionally having from 1 to 4 hydroxyl groups optionally being protected, and X 5  is YNR 1  R 3 , wherein Y and R 1  are the same as defined above, and R 3  is a C 1-6  alkyl group or a C 1-5  acyl group optionally having from 1 to 5 hydroxyl groups optionally being protected, which comprises treating an organic bismuth derivative represented by formula (I'-1): ##STR23## wherein X 4  is YNR 1  H, wherein Y and R 1  are the same as defined above, and X 2  and X 3  are the same as defined above with a base, and then reacting it with a compound represented by formula (IV):   R.sup.3 X                                                  (IV)     wherein R 3  is the same as defined above, and X is a halogen atom.   
     
     
       9. A process of producing an organic bismuth derivative represented by formula (I-2) or its salt: ##STR24## wherein each of X 2  and X 3  is, independently of each other, a hydrogen atom, a C 1-4  alkyl group, a C 1-4  alkoxy group, a C 1-4  alkylsulfonyl group, a C 1-4  alkylcarbonyl group, a nitro group, a cyano group or YNR 1  R 2 , wherein Y is --SO 2  -- or --C(O)--, R 1  is a C 3-6  alkyl group which has from 2 to 5 hydroxyl groups optionally being protected, and R 2  is a hydrogen atom, a C 1-6  alkyl group or a C 1-5  acyl group optionally having from 1 to 5 hydroxyl groups optionally being protected, or R 1  and R 2 , together with each other, represent a C 2-6  cyclic alkylene optionally having from 1 to 4 hydroxyl groups optionally being protected, and X 7  is YNR 1  R 2 , wherein y, R 1  and R 2  are the same as defined above, which comprises treating an organic bismuth derivative represented by formula (I'-2): ##STR25## wherein X 6  is YNHR 2 , wherein Y and R 2  are the same as defined above, and X 2  and X 3  are the same as defined above with a base, and then reacting it with a compound represented by formula (V):   R.sup.1 X                                                  (V)     wherein R 1  is C 3-6  alkyl group which has from 2 to 5 hydroxyl groups optionally being protected, and X is a halogen atom.   
     
     
       10. A process of producing an organic bismuth derivative represented by formula (I-3): ##STR26## wherein X 9  is YNR 1  R 2 , wherein Y is --SO 2  -- or --C(O)--, and R 1  and R 2 , together with each other, represent a C 2-6  cyclic alkylene optionally having from 1 to 4 hydroxyl groups optionally being protected, and each of X 2  and X 3  is, independently of each other, a hydrogen atom, a C 1-4  alkyl group, a C 1-4  alkoxy group, a C 1-4  alkylsulfonyl group, a C 1-4  alkylcarbonyl group, a nitro group, a cyano group or YNR 1  R 2 , wherein Y is the same as defined above, R 1  is a C 3-6  alkyl group which has from 2 to 5 hydroxyl groups optionally being protected, and R 2  is a hydrogen atom, a C 1-6  alkyl group or a C 1-5  acyl group optionally having from 1 to 5 hydroxyl groups optionally being protected, or and R 2 , together with each other, represent a C 2-6  cyclic alkylene optionally having from 1 to 4 hydroxyl groups optionally being protected, which comprises treating an organic bismuth derivative represented by formula (I'-3): ##STR27## wherein X 8  is YNH 2 , wherein Y is the same as defined above, and X 2  and X 3  are the same as defined above with a base, and then reacting it with a compound represented by formula (VI):   X--R.sup.1 --R.sup.2 --X'                                  (VI)     wherein R 1  and R 2 , together with each other, represent a C 2-6  alkylene optionally having from 1 to 4 hydroxyl groups optionally being protected, and X and X' are halogen atoms.   
     
     
       11. A radiographic contrast medium containing the organic bismuth derivative or its salt according to claim 1 as an active ingredient. 
     
     
       12. The organic bismuth derivative or its salt according to claim 1, wherein each of X 2  and X 3  is a hydrogen atom, and X 1  represents YNR 1  R 2  wherein Y is --SO 2  --, R 1  is 2,3-hydroxy-1-propyl and R 2  is a hydrogen atom.